Eligibility criteria for pediatric patients who may benefit from anti SARS-CoV-2 monoclonal antibody therapy administration: an Italian inter-society consensus statement

AbstractThe fast diffusion of the SARS-CoV-2 pandemic have called for an equally rapid evolution of the therapeutic options.The Human recombinant monoclonal antibodies (mAbs) have recently been approved by the Food and Drug Administration (FDA) and by the Italian Medicines Agency (AIFA) in subjects aged ≥12 with SARS-CoV-2 infection and specific risk factors.Currently the indications are specific for the use of two different mAbs combination: Bamlanivimab+Etesevimab (produced by Eli Lilly) and Casirivimab+Imdevimab (produced by Regeneron).These drugs have shown favorable effects in adult patients in the initial phase of infection, whereas to date few data are available on their use in children.AIFA criteria derived from the existing literature which reports an increased risk of severe COVID-19 in children with comorbidities. However, the studies analyzing the determinants for progression to severe disease are mainly monocentric, with limited numbers and reporting mostly generic risk categories.Thus, the Italian Society of Pediatrics invited its affiliated Scientific Societies to produce a Consensus document based on the revision of the criteria proposed by AIFA in light of the most recent literature and experts’ agreement.This Consensus tries to detail which patients actually have the risk to develop severe disease, analyzing the most common comorbidities in children, in order to detail the indications for mAbs administration and to guide the clinicians in identifying eligible patients.

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The role of Helicobacter pylori in the process of 43 carcinogenesis by means of dysregulation of miRNA expression

Epidemiology and Infectious Diseases (Russian Journal) ◽

10.17816/eid40847 ◽

2014 ◽

Vol 19 (6) ◽

pp. 43-47

Author(s):

O. F Belaia ◽

E. V Volchkova ◽

O. A Paevskaya ◽

S. N Zuevskaya ◽

Yu. V Yudina ◽

...

Keyword(s):

Helicobacter Pylori ◽

Intracellular Signaling ◽

Severe Disease ◽

Biological Significance ◽

Cancer Of The Stomach ◽

Increased Risk ◽

New Directions ◽

Stomach Adenocarcinoma ◽

Few Data

Duodenal ulcer is associated with Helicobacter pylori almost in 90-100% of cases. Severe disease of the stomach - adenocarcinoma - is caused by infection with Helicobacter pylori in 70-90% of cases. Persons infected with this bacterium were proven statistically to be in group of the increased risk of the development of gastric cancer. Helicobacter pylori expresses a spectrum of virulence factors which cause dysregulation of intracellular signaling pathways in a host cell, that reduces the resistance to neoplastic transformation. In the review there are presented data about identified to the present time deregulated miRNAs associated with H.pylori diseases, including cancer of the stomach, and a few data on their biological significance. The growing number of studies confirming the involvement of miRNAs in various stages of carcinogenesis - from gastritis to the formation of metastases - demonstrates the importance of the new directions of the research.

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Monoclonal Antibody Therapy Protects Pharmacologically Immunosuppressed Mice from Lethal Infection with Influenza B Virus

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00284-20 ◽

2020 ◽

Vol 64 (9) ◽

Author(s):

Bindumadhav M. Marathe ◽

Guha Asthagiri Arunkumar ◽

Peter Vogel ◽

Philippe Noriel Q. Pascua ◽

Jeremy Jones ◽

...

Keyword(s):

Combination Treatment ◽

Influenza A ◽

Severe Disease ◽

Antibody Therapy ◽

Influenza B Virus ◽

Influenza B ◽

Virus Spread ◽

Increased Risk ◽

B Virus ◽

Immunosuppressed Mice

ABSTRACT Human influenza A and B viruses are highly contagious and cause similar illnesses and seasonal epidemics. Currently available antiviral drugs have limited efficacy in humans with compromised immune systems; therefore, alternative strategies for protection are needed. Here, we investigated whether monoclonal antibodies (MAbs) targeting hemagglutinin (HA) and/or neuraminidase (NA) proteins would protect immunosuppressed mice from severe infections with influenza B virus. Pharmacologically immunosuppressed BALB/c mice were inoculated with B/Brisbane/60/2008 (BR/08) influenza virus and were treated with a single dose of 1, 5, or 25 mg/kg of body weight per day of either an anti-HA MAb (1D2) or an anti-NA MAb (1F2) starting at 24 hours postinoculation (hpi). Monotherapy with 1D2 or 1F2 MAbs provided dose-dependent protection of mice, with decreased BR/08 virus replication and spread in the mouse lungs, compared with those of controls. Combination treatment with 1D2 and 1F2 provided greater protection than did monotherapy, even when started at 48 hpi. Virus spread was also efficiently restrained within the lungs, being limited to 6%, 10%, and 10% of that seen in active infection when treatment was initiated at 24, 48, and 72 hpi, respectively. In most cases, the expression of cytokines and chemokines was altered according to when treatment was initiated. Higher expression of proinflammatory IP-10 and MCP-1 in combination-treatment groups, but not in monotherapy groups, to some extent, promoted better control of virus spread within the lungs. This study demonstrates the potential value of MAb immunotherapy in treating influenza in immunocompromised hosts who are at increased risk of severe disease.

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Illness severity and risk of mental morbidities among patients recovering from COVID-19: a cross-sectional study in the Icelandic population

BMJ Open ◽

10.1136/bmjopen-2021-049967 ◽

2021 ◽

Vol 11 (7) ◽

pp. e049967

Author(s):

Karen Sól Saevarsdóttir ◽

Hildur Ýr Hilmarsdóttir ◽

Ingibjörg Magnúsdóttir ◽

Arna Hauksdóttir ◽

Edda Bjork Thordardottir ◽

...

Keyword(s):

Severe Disease ◽

Symptom Burden ◽

Cross Sectional Study ◽

Illness Severity ◽

University Education ◽

Adjusted Relative Risk ◽

Sectional Study ◽

Cross Sectional ◽

Symptoms Of Depression ◽

Increased Risk

ObjectiveTo test if patients recovering from COVID-19 are at increased risk of mental morbidities and to what extent such risk is exacerbated by illness severity.DesignPopulation-based cross-sectional study.SettingIceland.ParticipantsA total of 22 861 individuals were recruited through invitations to existing nationwide cohorts and a social media campaign from 24 April to 22 July 2020, of which 373 were patients recovering from COVID-19.Main outcome measuresSymptoms of depression (Patient Health Questionnaire), anxiety (General Anxiety Disorder Scale) and posttraumatic stress disorder (PTSD; modified Primary Care PTSD Screen for DSM-5) above screening thresholds. Adjusting for multiple covariates and comorbidities, multivariable Poisson regression was used to assess the association between COVID-19 severity and mental morbidities.ResultsCompared with individuals without a diagnosis of COVID-19, patients recovering from COVID-19 had increased risk of depression (22.1% vs 16.2%; adjusted relative risk (aRR) 1.48, 95% CI 1.20 to 1.82) and PTSD (19.5% vs 15.6%; aRR 1.38, 95% CI 1.09 to 1.75) but not anxiety (13.1% vs 11.3%; aRR 1.24, 95% CI 0.93 to 1.64). Elevated relative risks were limited to patients recovering from COVID-19 that were 40 years or older and were particularly high among individuals with university education. Among patients recovering from COVID-19, symptoms of depression were particularly common among those in the highest, compared with the lowest tertile of influenza-like symptom burden (47.1% vs 5.8%; aRR 6.42, 95% CI 2.77 to 14.87), among patients confined to bed for 7 days or longer compared with those never confined to bed (33.3% vs 10.9%; aRR 3.67, 95% CI 1.97 to 6.86) and among patients hospitalised for COVID-19 compared with those never admitted to hospital (48.1% vs 19.9%; aRR 2.72, 95% CI 1.67 to 4.44).ConclusionsSevere disease course is associated with increased risk of depression and PTSD among patients recovering from COVID-19.

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491. Aerosol-Generating Medical Procedures: Transmission of SARS-CoV-2 and Emerging Viruses

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.684 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S312-S312

Author(s):

Seth D Judson ◽

Vincent J Munster

Keyword(s):

High Risk ◽

Severe Disease ◽

Experimental Studies ◽

Virus Transmission ◽

Nosocomial Transmission ◽

Medical Procedures ◽

Emerging Viruses ◽

Zoonotic Viruses ◽

Increased Risk ◽

Hospital Acquired

Abstract Background During the pandemic of coronavirus disease 2019 (COVID-19), many questions arose regarding risks for hospital-acquired or nosocomial transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Aerosol generating medical procedures (AGMPs), techniques that can generate infectious, virus-laden aerosols, could potentially amplify transmission among healthcare workers (HCWs). Thus, it was widely recommended that HCWs use airborne precautions when performing AGMPs. However, in clinical settings it is often unclear what procedures constitute AGMPs and how the risk varies by procedure or pathogen. We set out to further define AGMPs and assess the risk for nosocomial transmission of SARS-CoV-2 and other high-risk viruses via AGMPs. Methods We identified potential AGMPs and emerging viruses that were high-risk for nosocomial transmission through reviewing experimental and clinical data. Potential AGMPs were those associated with previous virus transmission or mechanically capable of transmission. High-risk viruses were defined as those that cause severe disease in humans for which limited therapies or interventions exist, are infectious via aerosols in humans or non-human primates (NHPs), found in the respiratory tract of infected humans or NHPs, and had previous evidence of nosocomial transmission. Results We identified multiple potential AGMPs, which could be divided into those that generate aerosols or induce a patient to form aerosols, as well as eight families of high-risk viruses. All of the viruses were emerging zoonotic RNA viruses. In the family Coronaviridae, we identified potential evidence for SARS-CoV-1, MERS-CoV, and SARS-CoV-2 transmission via AGMPs. SARS-CoV-1 and SARS-CoV-2 were also found to be similarly stable when aerosolized. Conclusion Multiple emerging zoonotic viruses pose a high risk for nosocomial transmission through a variety of AGMPs. Given the similar stability of SARS-CoV-2 with SARS-CoV-1 when aerosolized and prior nosocomial transmission of SARS-CoV-1 via AGMPs, we suspect that certain AGMPs pose an increased risk for SARS-CoV-2 transmission. Additional experimental studies and on-site clinical sampling during AGMPs are necessary to further risk stratify AGMPs. Disclosures All Authors: No reported disclosures

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270. Clinical Outcomes of Ceftriaxone versus Penicillin G for Complicated Viridans Group Streptococci Bacteremia

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.314 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S137-S137

Author(s):

Stephanie Wo ◽

Yanina Dubrovskaya ◽

Justin Siegfried ◽

John Papadopoulos ◽

Shin-Pung Jen

Keyword(s):

Clinical Outcomes ◽

Hospital Readmission ◽

Protective Factor ◽

Primary Outcome ◽

Bloodstream Infections ◽

Penicillin G ◽

Eligibility Criteria ◽

Extended Spectrum Beta Lactamase ◽

Increased Risk ◽

Viridans Group Streptococci

Abstract Background Viridans group streptococci (VGS) is an infrequent yet significant cause of bloodstream infections, and complicated cases may require prolonged antibiotic therapy. Ceftriaxone (CTX) and penicillin G (PCN G) are both considered first line options for VGS infections, but comparisons between these agents are limited. We evaluated the clinical outcomes amongst patients treated with CTX and PCN G for complicated VGS bacteremia. Methods This was a single-center, retrospective study of adult patients with ≥1 positive VGS blood culture who were treated with either CTX or PCN G/ampicillin (both included in PCN G arm) between January 2013 and June 2019. The primary outcome was a composite of safety endpoints, including hospital readmission due to VGS or an adverse event (AE) from therapy, Clostridioides difficile infections, treatment modification or discontinuation due to an antibiotic-related AE, and development of extended-spectrum beta lactamase resistance. Secondary outcomes included the individual safety endpoints, VGS bacteremia recurrence, hospital readmission, and all-cause mortality. Results Of 328 patients screened for inclusion, 94 patients met eligibility criteria (CTX n= 64, PCN G n=34). Median age was 68 years (IQR 56–81) and 68% were male. Study patients did not present with critical illness, as reflected by a median Pitt bacteremia score of 0 in the CTX and 1 in the PCN G arms, P=0.764. Streptococcus mitis was the most common VGS isolate and infective endocarditis (IE) was the predominant source of infection. CTX was not significantly associated with increased risk of the primary outcome (14% vs. 27%; P= 0.139). The driver of the composite outcome was hospital readmission due to VGS bacteremia or therapy complications. Results were similar in the subgroup of patients with IE (12.5% vs. 23.5%). No secondary endpoints differed significantly between groups. On multivariate analysis, source removal was a protective factor of the primary outcome (OR 0.1; 95% CI 0.020–0.6771; P= 0.017). Conclusion Despite potential safety concerns with the prolonged use of CTX in complicated VGS bacteremia, this study did not demonstrate a higher rate of treatment failure, adverse events, or resistance. These findings warrant further exploration. Disclosures All Authors: No reported disclosures

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Gastrostomy Tubes Placed in Children With Neurologic Impairment: Associated Morbidity and Mortality

Journal of Child Neurology ◽

10.1177/08830738211000179 ◽

2021 ◽

pp. 088307382110001

Author(s):

Jody L. Lin ◽

Joseph Rigdon ◽

Keith Van Haren ◽

MyMy Buu ◽

Olga Saynina ◽

...

Keyword(s):

Severe Pneumonia ◽

Sensitivity Analyses ◽

Tube Placement ◽

Composite Outcome ◽

Eligibility Criteria ◽

Risk Of Death ◽

Cox Proportional Hazard ◽

Neurologic Impairment ◽

Increased Risk ◽

The Impact

Background: Gastrostomy tube (G-tube) placement for children with neurologic impairment with dysphagia has been suggested for pneumonia prevention. However, prior studies demonstrated an association between G-tube placement and increased risk of pneumonia. We evaluate the association between timing of G-tube placement and death or severe pneumonia in children with neurologic impairment. Methods: We included all children enrolled in California Children’s Services between July 1, 2009, and June 30, 2014, with neurologic impairment and 1 pneumonia hospitalization. Prior to analysis, children with new G-tubes and those without were 1:2 propensity score matched on sociodemographics, medical complexity, and severity of index hospitalization. We used a time-varying Cox proportional hazard model for subsequent death or composite outcome of death or severe pneumonia to compare those with new G-tubes vs those without, adjusting for covariates described above. Results: A total of 2490 children met eligibility criteria, of whom 219 (9%) died and 789 (32%) had severe pneumonia. Compared to children without G-tubes, children with new G-tubes had decreased risk of death (hazard ratio [HR] 0.47, 95% confidence interval [CI] 0.39-0.55) but increased risk of the composite outcome (HR 1.21, CI 1.14-1.27). Sensitivity analyses using varied time criteria for definitions of G-tube and outcome found that more recent G-tube placement had greater associated risk reduction for death but increased risk of severe pneumonia. Conclusion: Recent G-tube placement is associated with reduced risk of death but increased risk of severe pneumonia. Decisions to place G-tubes for pulmonary indications in children with neurologic impairment should weigh the impact of severe pneumonia on quality of life.

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Use of monoclonal antibody therapy for nosocomial SARS-CoV-2 infection in patients at high risk for severe COVID-19: experience from a tertiary-care hospital in Germany

Infection ◽

10.1007/s15010-021-01657-y ◽

2021 ◽

Author(s):

Johanna Koehler ◽

Barbara Ritzer ◽

Simon Weidlich ◽

Friedemann Gebhardt ◽

Chlodwig Kirchhoff ◽

...

Keyword(s):

High Risk ◽

Tertiary Care Hospital ◽

Severe Disease ◽

Treatment Options ◽

Tertiary Care ◽

Antibody Therapy ◽

Additional Treatment ◽

Care Hospital ◽

Cross Sectional ◽

Asymptomatic Patients

AbstractAdditional treatment options for coronavirus disease (COVID-19) are urgently needed, particularly for populations at high risk of severe disease. This cross-sectional, retrospective study characterized the outcomes of 43 patients with nosocomial severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection with and without treatment using monoclonal SARS-CoV-2 spike antibodies (bamlanivimab or casirivimab/imdevimab). Our results indicate that treatment with monoclonal antibodies results in a significant decrease in disease progression and mortality when used for asymptomatic patients with early SARS-CoV-2 infection.

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Diabetes and COVID19: a bidirectional relationship

European Journal of Clinical Nutrition ◽

10.1038/s41430-021-00961-y ◽

2021 ◽

Author(s):

Ranjit Unnikrishnan ◽

Anoop Misra

Keyword(s):

Clinical Care ◽

Severe Disease ◽

Respiratory Involvement ◽

Pancreatic Damage ◽

Increased Risk ◽

Bidirectional Relationship ◽

Rapid Spread ◽

Relationship Of ◽

The Relationship ◽

New Onset

AbstractThe advent and rapid spread of the coronavirus disease-2019 (COVID19) pandemic across the world has focused attention on the relationship of commonly occurring comorbidities such as diabetes on the course and outcomes of this infection. While diabetes does not seem to be associated with an increased risk of COVID19 infection per se, it has been clearly demonstrated that the presence of hyperglycemia of any degree predisposes to worse outcomes, such as more severe respiratory involvement, ICU admissions, need for mechanical ventilation and mortality. Further, COVID19 infection has been associated with the development of new-onset hyperglycemia and diabetes, and worsening of glycemic control in pre-existing diabetes, due to direct pancreatic damage by the virus, body’s stress response to infection (including cytokine storm) and use of diabetogenic drugs such as corticosteroids in the treatment of severe COVID19. In addition, public health measures taken to flatten the pandemic curve (such as lockdowns) can also adversely impact persons with diabetes by limiting their access to clinical care, healthy diet, and opportunities to exercise. Most antidiabetic medications can continue to be used in patients with mild COVID19 but switching over to insulin is preferred in severe disease.

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Baseline T-lymphocyte subset absolute counts can predict both outcome and severity in SARS-CoV-2 infected patients: a single center study

Scientific Reports ◽

10.1038/s41598-021-90983-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Marco Iannetta ◽

Francesco Buccisano ◽

Daniela Fraboni ◽

Vincenzo Malagnino ◽

Laura Campogiani ◽

...

Keyword(s):

Hospital Mortality ◽

T Lymphocyte ◽

Lymphocyte Subsets ◽

Severe Disease ◽

Laboratory Data ◽

Lymphocyte Subset ◽

Multivariable Logistic Regression Analysis ◽

Double Positive ◽

Increased Risk ◽

T Lymphocyte Subset

AbstractThe aim of this study was to evaluate the role of baseline lymphocyte subset counts in predicting the outcome and severity of COVID-19 patients. Hospitalized patients confirmed to be infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) were included and classified according to in-hospital mortality (survivors/nonsurvivors) and the maximal oxygen support/ventilation supply required (nonsevere/severe). Demographics, clinical and laboratory data, and peripheral blood lymphocyte subsets were retrospectively analyzed. Overall, 160 patients were retrospectively included in the study. T-lymphocyte subset (total CD3+, CD3+ CD4+, CD3+ CD8+, CD3+ CD4+ CD8+ double positive [DP] and CD3+ CD4− CD8− double negative [DN]) absolute counts were decreased in nonsurvivors and in patients with severe disease compared to survivors and nonsevere patients (p < 0.001). Multivariable logistic regression analysis showed that absolute counts of CD3+ T-lymphocytes < 524 cells/µl, CD3+ CD4+ < 369 cells/µl, and the number of T-lymphocyte subsets below the cutoff (T-lymphocyte subset index [TLSI]) were independent predictors of in-hospital mortality. Baseline T-lymphocyte subset counts and TLSI were also predictive of disease severity (CD3+ < 733 cells/µl; CD3+ CD4+ < 426 cells/µl; CD3+ CD8+ < 262 cells/µl; CD3+ DP < 4.5 cells/µl; CD3+ DN < 18.5 cells/µl). The evaluation of peripheral T-lymphocyte absolute counts in the early stages of COVID-19 might represent a useful tool for identifying patients at increased risk of unfavorable outcomes.

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